Osteoarthritis is reaching epidemic proportions in the United States [1]. Current clinical imaging modalities are unable to reliably diagnose cartilage degeneration prior to the onset of irreversible changes [2-5]. This is a major obstacle to the development and assessment of new strategies to delay or prevent the onset of disabling osteoarthritis through early intervention disease modifying treatments. The effectiveness of optical coherence tomography (OCT), a novel nondestructive optical imaging technology, for clinical diagnosis of early cartilage degeneration is under evaluation in the parent proposal, "Enhanced Clinical Diagnosis of Early Osteoarthritis". OCT is capable of imaging articular cartilage at microscopic resolutions in near real time to detect structural changes within grossly normal appearing articular cartilage [6-9]. The PI has also shown that OCT can be used clinically during arthroscopic surgery to detect changes to cartilage matrix birefringence predictive of potentially reversible early metabolic incompetence [10]. While these findings support the feasibility of using diagnostic imaging to identify cartilage degeneration early enough for potential disease modifying treatment, OCT cannot visualize cartilage through intact skin and evaluates only the superficial 1-2 millimeters of articular cartilage. Multi-parametric magnetic resonance imaging (MRI) can also provide information about articular cartilage structure and biochemical integrity [11-18]. Advantages of MRI include noninvasive imaging and the ability to image the full thickness of the cartilage as well as bone and other joint tissues. As a noninvasive technology, MRI can be more broadly applied for screening and for longitudinal follow-up studies requiring quantitative monitoring and evaluation of potential disease modifying interventions. However, the relatively gross resolutions of standard MRI (<500 <m) do not approach the high spatial resolution of OCT (<10 <m). As such, evaluation of cartilage microstructural detail through MRI remains elusive. We will explore two strategies for improving the contrast and spatial resolution of MRI cartilage evaluation closer to that of OCT: (1) the use of novel cartilage imaging sequences and (2) the use of higher magnet field strengths. Collaborations with two new investigators who have innovative expertise in these areas are proposed to build an interdisciplinary team addressing the scientific areas of Soft Tissue Biology-Imaging Technologies. Successful correlation of OCT measures of early cartilage degeneration with MRI would significantly enhance the scope and impact of the parent grant towards translation of new imaging technologies into clinical use for improved diagnosis and staging of early articular cartilage degeneration. [unreadable] [unreadable] [unreadable]